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Comparing therapies for canine hyperadrenocorticism

Dr. Edward C. Feldman lectured at the 2007 American College of Veterinary Internal Medicine (ACVIM) Forum in Seattle on "Medical Management of Canine Hyperadrenocorticism: A Comparison of Trilostane to Mitotane." Here are some relevant points:

Polyuria is the most worrisome and life-threatening aspect of hyperadrenocorticism in the context of owners who will not or cannot tolerate a dog that is no longer housebroken due to large volumes of urine produced secondary to a condition like hyperadrenocorticism. Therefore, the concern that encourages most owners to consider treatment is their dog's polyuria.

No dog should be treated for hyperadrenocorticism — a clinical condition — unless there are obvious clinical signs consistent with the diagnosis and that are worrisome to the owner. But once a dog has clinical signs and the diagnosis is confirmed, the owner should consider treatment.

Medical therapy using o,p'-DDD

o,p'-DDD (Lysodren, Mitotane) is a cytotoxic agent related to the insecticide DDT. This drug has been used successfully by veterinarians for the treatment of canine PDH for well over 30 years. The drug has a reputation of being toxic, and that has has limited its use. However, that reputation for toxicity should merely increase respect for the drug. Used correctly, it is safe, cost effective and efficacious.

No dog with a poor appetite should ever be treated medically for PDH.

Induction protocol

Therapy with o,p'-DDD always should be initiated at home, with the owner administering 25 mg/kg, given BID. Glucocorticoids are neither routinely administered nor dispensed. Rather, the owner should receive thorough instructions on the actions of o,p'-DDD. Then, the owner is instructed to begin reducing the dog's food allotment by one-third beginning the day before o,p'-DDD is begun.

Because we always begin therapy on a Sunday, we have owners give their dog two-thirds of its normal food allotment, one-third each morning and again one-third each evening, beginning on the Saturday preceding the first day of therapy. This should make the typical polyphagic dog quite hungry.

Lysodren administration should be continued BID until any of the following are observed: 1) the polydipsic dog's daily water consumption approaches 60 ml/kg; 2) the dog simply takes longer to consume a meal and certainly if it develops partial or complete anorexia/inappetence; 3) vomiting; 4) diarrhea or 5) unusual listlessness. Any of these observations demands that an owner stop daily o,p'-DDD therapy and have the dog examined by the veterinarian.

The single most reliable and consistent indicator for having reached the endpoint of this induction phase of therapy is appetite reduction. Any reduction in appetite indicates that the induction phase has been completed. The water intake in polydipsic dogs may decrease in as few as two days or as many as 35 days (average is five to 14 days), but is less consistent in determining therapeutic endpoint. Using appetite to determine endpoint also decreases the risk of ever observing vomiting or diarrhea secondary to the use of o,p'-DDD.

Lysodren is quite successful in eliminating the clinical signs of hyperadrenocorticism by reducing serum cortisol concentrations. This therapeutic approach requires close communication between owner and veterinarian. Either a veterinarian or technician should call the owner each day beginning with the second day of therapy during the initial week, or induction phase, of o,p'-DDD administration. The owner, after being contacted several days in a row, typically becomes quite impressed by the veterinarian's concern.

They usually will begin to observe their dog closely. Once a dog demonstrates any reduction in appetite, it can be examined by the veterinarian. An ACTH-stimulation test can be done at that same visit. In addition to making daily calls, the veterinarian should see the dog no later than eight days after beginning therapy, if an owner has not seen appetite reduction. At this time, a thorough history, physical examination and an ACTH response test should be performed. Dogs responding clinically to the medication (or if the owner is not certain about response) should have further therapy withheld until results of the ACTH response test can be evaluated.